Mary M. Robertson

The international prevalence, epidemiology, and clinical phenomenology of Tourette syndrome: A cross-cultural perspective

The overall international prevalence of Tourette syndrome (TS) is 1% in the majority of cultures of the world. Both TS and tics are certainly more obvious and may be more common in younger people. Moreover, TS is seen less frequently in some cultures. However, in all cultures where it has been reported, the phenomenology is similar, highlighting the biological underpinnings of the disorder. This article reviews the international prevalence, epidemiology, and clinical phenomenology of TS, from a cross-cultural perspective.

The Tourette Syndrome Diagnostic Confidence Index Development and clinical associations

Background: The clinical characteristics of Tourette syndrome (TS) present challenges for the systematic determination of whether individuals are affected and severity. Vocal and motor tics wax and wane, decrease over time, and may be voluntarily suppressible, and therefore may be absent at interview. Current instruments measure symptoms at interview or rate symptom severity only. Method:— To minimize error in case ascertainment and produce an instrument measuring lifetime likelihood of having had TS, clinical members of the American Tourette Syndrome Association International Genetic Collaboration developed the Diagnostic Confidence Index (DCI). The expert group worked collaboratively with progressive revision in consensus workshops using existing diagnostic criteria as guidelines. The DCI produces a score from 0 to 100 that is a measure of the likelihood of having or ever having had TS. Results: The DCI was administered to 280 consecutive patients with TS attending a TS clinic; 264 (94%) completed it, indicating high feasibility and acceptability. Its correlation with other instruments and associations with psychopathology provide support for its being a lifetime measure of TS. Conclusions: The DCI is a useful, practicable instrument in the clinic or research practice allowing an assessment of lifetime likelihood of TS. Further work is needed to test the DCI’s psychometric properties, such as its validity and reliability in populations of interest.

Executive function in Tourette's syndrome and obsessive-compulsive disorder

BACKGROUND Cognitive performance was compared in the genetically and neurobiologically related disorders of Tourettes syndrome (TS) and obsessive-compulsive disorder (OCD), in three domains of executive function: planning, decision-making and inhibitory response control. METHOD Twenty TS patients, twenty OCD patients and a group of age- and IQ-matched normal controls completed psychometric and computerized cognitive tests and psychiatric rating scales. The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal disorders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making. RESULTS Compared to controls, OCD patients showed selective deficits in pattern recognition memory and slower responding in both pattern and spatial recognition, impaired extra-dimensional shifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. In contrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting, and decision-making. Neither group was impaired in planning. Direct comparisons between the TS and OCD groups revealed significantly different greater deficits for recognition memory latency and Go/No-go reversal for the OCD group, and quality of decision-making for the TS group. CONCLUSIONS TS and OCD show both differences (recognition memory, decision-making) and similarities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in the OCD group contrasted with their intact performance on other tests of executive function, such as planning and decision-making, and suggested only limited involvement of frontal lobe dysfunction, possibly consistent with OCD symptomatology.

Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis.

Background: The classical neurological disorder after group A β haemolytic streptococcal infection is Sydenham’s chorea. Recently a tic disorder occurring after group A streptococcal infection has been described and termed PANDAS (paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). It is proposed that antibodies induced after group A streptococcal infection react with basal ganglia neurones in Sydenham’s chorea and PANDAS. Anti-basal ganglia antibodies (ABGA) are present in most cases of acute Sydenham’s chorea, but rarely in controls. Objective: To investigate the hypothesis that Tourette’s syndrome may be associated with group A streptococcal infection and ABGA. Methods: 100 patients with Tourette’s syndrome (DSM-IV-TR) were enrolled in a cross sectional study. Children with neurological disease (n = 50) and recent uncomplicated streptococcal infection (n = 40), adults with neurological disease (n = 50), and healthy adults (n = 50) were studied as controls. Recent group A streptococcal infection was defined using antistreptolysin O titre (ASOT). ABGA were detected using western immunoblotting and indirect immunofluorescence. Results: ASOT was raised in 64% of children with Tourette’s syndrome compared with 15% of paediatric neurological disease controls (p < 0.0001), and in 68% of adults with Tourette’s syndrome compared with 12% of adult neurological controls and 8% of adult healthy controls (p < 0.05). Western immunoblotting showed positive binding in 20% of children and 27% of adults with Tourette’s syndrome, compared with 2–4% of control groups (p < 0.05). The most common basal ganglia binding was to a 60 kDa antigen, similar to the proposed antigen in Sydenham’s chorea. Indirect immunofluorescence revealed autoantibody binding to basal ganglia neurones. Serological evidence of recent group A streptococcal infection, assessed by a raised ASOT, was detected in 91% (21/23) of Tourette’s syndrome patients with positive ABGA compared with 57% (44/77) with negative ABGA (p < 0.01). Conclusions: The results support a role of group A streptococcal infection and basal ganglia autoimmunity in a subgroup of patients with Tourette’s syndrome and suggest a pathogenic similarity between Sydenham’s chorea and some patients with Tourette’s syndrome.

Thalamic deep brain stimulation for treatment-refractory Tourette syndrome: two-year outcome.

Background: Eighteen patients with severe and refractory Tourette syndrome (TS) underwent bilateral thalamic deep brain stimulation (DBS). Objective: To assess the long-term outcome on tics, behavioral symptoms, and cognitive functions in the largest case series of thalamic DBS for TS to date. Methods: In this prospective cohort study, 15 of the original 18 patients were evaluated before and after surgery according to a standardized protocol that included both neuropsychiatric and neuropsychological assessments. Results: In addition to marked reduction in tic severity (p = 0.001), 24-month follow-up ratings showed improvement in obsessive-compulsive symptoms (p = 0.009), anxiety symptoms (p = 0.001), depressive symptoms (p = 0.001), and subjective perception of social functioning/quality of life (p = 0.002) in 15 of 18 patients. There were no substantial differences on measures of cognitive functions before and after DBS. Conclusions: At 24-month follow-up, tic severity was improved in patients with intractable Tourette syndrome (TS) who underwent bilateral thalamic deep brain stimulation. Available data from 15 of 18 patients also showed that neuropsychiatric symptoms were improved and cognitive performances were not disadvantaged. Controlled studies on larger cohorts with blinded protocols are needed to verify that this procedure is effective and safe for selected patients with TS. Level of evidence: This study provides class IV evidence that bilateral thalamic deep brain stimulation reduces global tic severity measured 24 months after implantation in patients with severe intractable Tourette syndrome.

A clinical study of Gilles de la Tourette syndrome in the United Kingdom.

The clinical features of 53 British-born patients with Gilles de la Tourette syndrome are described. The mean age at onset of body tics was seven years and for vocalisations 11 years. Coprolalia was present in 39%, copropraxia in 21%, echolalia in 46% and echopraxia in 21%. Complicated antics and mannerisms were also common, often involving the compulsive touching of objects or self-injurious behaviour. Forty-six per cent of cases had a family history of tics in a single close relative and in two individuals a further member of the family had Gilles de la Tourette syndrome. Focal dystonia was present in four patients who had never received neuroleptics drugs and chorea was seen in two other untreated patients. In three patients acoustic startle consistently induced brief eye blink followed by a whole body jerk or jump. Rapid repetitive movements of the hands increased the frequency and severity of tics in 13 patients, but the performance of mental arithmetic under time pressure had a much more unpredictable effect. Electroencephalographic abnormalities occurred in eight (13%) but no definite CT brain scan abnormalities were detected. The incidence of left handedness did not differ from that in the general population and no evidence to suggest organic impairment was found on neuropsychological testing. This study provides no support for the notion that Gilles de la Tourette syndrome is a degenerative disorder of the central nervous system but provides some evidence for heterogeneity.

Clinical features and associated psychopathology in a Tourette syndrome cohort

Objective – This study explored in detail the association between tic symptomatology, related clinical variables, and psychopathology in 91 consecutive adult TS subjects from a UK clinic.

Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder

The distribution of obsessive compulsive symptoms was compared in 16 individuals with primary obsessive compulsive disorder (OCD) and 16 individuals with Gilles de la Tourette syndrome (GTS) and associated obsessive compulsive behaviors (OCB). The two groups showed significant differences in the distribution of OC symptomatology. Furthermore, those OCD probands who shared a similar symptom profile with GTS individuals all had a positive family history of OCD. All of the other OCD probands were isolated cases. Implications of this finding on the etiology and pathogenesis of the two disorders are discussed.

Gilles de la Tourette syndrome and deep brain stimulation

Gilles de la Tourette Syndrome (GTS) is characterized by multiple motor and one or more vocal/phonic tics. Psychopathology and co‐morbidity occur in approximately 80–90% of clinical cohorts. The most common psychopathologies are attention deficit hyperactivity disorder, obsessive‐compulsive behaviours, obsessive‐compulsive disorder, depression, anxiety and certain behavioural disorders. In severe GTS patients who are refractory to medication and other therapies, deep brain stimulation (DBS) is investigated. To date there have been some 50–55 patients who have received DBS in 19 centres worldwide. Nine different brain targets in the thalamus, the pallidum, and the ventral caudate and anterior internal capsule have been stimulated. This paper reviews critically and in detail all studies published to date. Only two studies on just a few patients fulfil some of the evidence‐based criteria. DBS for GTS is therefore still highly experimental.

Bilineal transmission in Tourette's syndrome families

We assessed the frequency of bilineal (from maternal and paternal sides) transmission of Tourettes syndrome (TS) in two groups of pedigrees: (1) 39 high-density families in which five or more relatives were reported to have TS, and (2) the families of 39 consecutively ascertained probands referred for evaluation of TS. We used two designations for the TS phenotype (tics, tics or obsessive-compulsive behavior [OCB]), and we attempted to verify bilineal transmission with direct examinations. For the high-density pedigrees, bilineal transmission was evident in 33% (considering tics) and 41% (considering tics or OCB) of families, which was confirmed by examination in 77% of the kindreds. For the consecutive pedigrees, bilineal transmission was seen in 15% (tics) and 26% (tics or OCB) of families, which was verified by examination in 66% of the kindreds. Both parents of the proband were affected (tics or OCB) in 38% of the high-density pedigrees and 10% of the consecutive pedigrees. For the high-density families only, the frequency of bilineal transmission appeared to be related to the probands severity of TS, and for both pedigree groups, the frequency of both parents being affected was higher in families in which the probands symptoms were most severe. Our findings support the contention that bilineal transmission and homozygosity are common in TS. These genetic phenomena might play a role in determining severity of illness and may explain current difficulties in localizing the gene defect by linkage analysis.